HEPATITIS C COOPERATIVE RESEARCH CENTERS
RELEASE DATE: August 5, 2004
RFA Number: RFA-AI-04-028
Update: The following update relating to this announcement has been issued:
April 7, 2009 - This RFA has been reissued as (RFA-AI-09-025).
EXPIRATION DATE: November 23, 2004
Department of Health and Human Services (DHHS)
PARTICIPATING ORGANIZATION:
National Institutes of Health (NIH)
(http://www.nih.gov)
COMPONENTS OF PARTICIPATING ORGANIZATION:
National Institute of Allergy and Infectious Diseases (NIAID)
(http://www.niaid.nih.gov)
National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK)
(http://www.niddk.nih.gov)
National Institute on Drug Abuse (NIDA)
(http://www.nida.nih.gov)
CATALOGUE OF FEDERAL DOMESTIC ASSISTANCE NUMBERS:
No. 93.855, Immunology, Allergy, and Transplantation Research
No. 93.856, Microbiology and Infectious Diseases Research
No. 93.848, Digestive Diseases and Nutrition Research
No. 93.273, Drug Abuse Research Programs
LETTER OF INTENT RECEIPT DATE: October 22, 2004
APPLICATION RECEIPT DATE: November 22, 2004
THIS RFA CONTAINS THE FOLLOWING INFORMATION
o Purpose of this RFA
o Research Objectives
o Mechanism of Support
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Supplementary Instructions
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations
PURPOSE OF THIS RFA
The National Institute of Allergy and Infectious Diseases (NIAID), the
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and
the National Institute on Drug Abuse (NIDA) invite applications for the
establishment of multi-project Hepatitis C Cooperative Research Centers (HC
CRCs).
The purpose of this RFA is to foster and stimulate high-quality, multi-
disciplinary collaborative research that is focused on developing tools to
prevent and cure hepatitis C virus (HCV) infection and disease. The goal is
to generate research findings that will be directly applicable, particularly
to the development of vaccines and (immune) therapeutics. This RFA calls for
new approaches for the rapid utilization and validation of research findings
using a combination of basic, animal model, and clinical research approaches.
The HC CRCs are encouraged to engage in early translational research so as to
address hepatitis C public health needs. Together, the HC CRCs will form a
consortium to: 1) conduct research of direct relevance to the objectives
outlined; 2) foster interactions among established hepatitis C investigators;
and 3) support Pilot Projects to evaluate new promising approaches related to
this RFA.
RESEARCH OBJECTIVES
Background
At least 2% of the world’s population is infected with Hepatitis C virus
(HCV); over 75% of infections never resolve, resulting in persistent virus
carriage. Over time, this chronic infection can lead to liver fibrosis and,
progressively, to severe and fatal diseases including liver cirrhosis and
primary liver cancer. The Institute of Medicine classifies HCV as an emerging
disease agent in the USA, with 1.7 million individuals already chronically
infected and 30,000 more, newly infected, every year (IOM report, 1992). In
the USA, the economic cost of this medical burden is estimated at
approximately $1.0 billion per year.
At present, in the USA, almost all transmission stems from the use of
contaminated needles in intravenous drug abuse. Thus, most new infections are
likely to occur among relatively young people. HCV infection resulting from
intravenous drug abuse is frequently complicated by co-infection with HIV. In
particular, chronic HCV infection and associated liver disease are reported
to develop at a higher rate in the presence of HIV.
HCV is an RNA virus which circulates as a complex mixture of related but
genetically heterogeneous quasi-species. There are at least 6 distinct
genotypes of HCV, which further adds to the heterogeneity and which may
influence differences in clinical outcomes - such as persistence, chronic
liver disease, immune responses, and the response to interferon treatment.
Currently, the treatment of choice for hepatitis C is long-acting alpha
interferon given in combination with the antiviral drug, ribavirin. However,
there are wide differences in the response to alpha interferon depending on
the genotype of HCV. The lowest response rate (only ~ 46%), is observed in
patients infected with HCV genotype-1, which is the genotype most prevalent
in the USA. Studies also indicate a lower cure rate among African Americans,
a population group which has a significantly higher rate of chronic infection
than others in the USA.
The development of a vaccine to prevent infection by HCV is beset by complex
problems. Immune pressure leads to continual selection, and diversification,
of viral variants that escape the host defenses. In addition, HCV directly
inhibits both innate and adaptive host immune responses. Even in the small
proportion of infected individuals who clear the infection there is usually
insufficient immunity to prevent a subsequent re-infection. On the other
hand, vaccine studies in chimpanzees have shown that induction of high titers
of antibodies against virus envelope proteins E1 and E2 is associated with
reduced severity of liver disease. Particularly encouraging for vaccine
development are findings from prospective studies in intravenous drug users,
that individuals who clear an initial HCV infection are less susceptible to
viral persistence following a subsequent infection.
Like several other viruses, HCV has evolved multiple strategies for blocking
interferon responses, simultaneously compromising both innate and adaptive
immune responses against it. Current evidence indicates that broad HCV-
specific T cell responses can occur in infection, and that the breadth of the
response corresponds with more benign outcomes following infection. However,
it is not clear what particular responses are significant in terms of
protective immunity, and why the responses vary within and among,
individuals.
Finally, recent HCV-replicon technology now allows in vitro screening for
antiviral drugs that target virus RNA replication, but not yet for those that
might interfere with the subsequent steps of virus morphogenesis and with
infection. The development of in vitro systems for virus propagation, and
small-animal infection models, would greatly facilitate the ultimate goals of
developing new therapies and vaccines against HCV.
Objectives and Scope
This RFA will support integrated projects to study the virus-host
interactions that determine the outcome of infection, treatment associated
recovery, and pathogenesis. These projects include: multi-disciplinary
research for understanding mechanisms; in vivo studies for validation of in
vitro findings; the use of particular patient cohorts and/or specimens from
patients in clinical research relevant to these objectives; and early
development and preclinical evaluation of vaccine and therapeutic strategies.
Applications should address specifically one or more of the objectives listed
below and may address other closely related questions.
1. Elucidate the mechanisms and key steps by which HCV deregulates and evades
the host immune response at the time of initial infection and during chronic
infection, e.g., the role of HCV proteins in blunting the innate immune
response, inhibiting dendritic cell maturation, or setting up an anergic
state.
2. Identify early determinants of spontaneous clearance of infection,
including specific T-cell and B-cell responses, as compared with, and in
contrast to, lack of clearance.
3. Examine the role of immune responses associated with delayed and more
benign outcomes of chronic HCV following multiple exposures to virus, e.g.,
in intravenous drug users, as compared to aggressive and severe outcomes.
4. Elucidate the role of host factors (including genetic) and viral factors
in the establishment and rate of progression of chronic infection and their
interactions with each other.
5. Construct prototype vaccine candidates to induce specific immune responses
to HCV - identified through human clinical studies, and predicted to be
important in viral clearance - and evaluate these responses in appropriate in
vitro and in vivo model systems.
6. Devise cell-culture systems for the synthesis of complete, infectious
particles, and determine their potential usefulness for research and
development.
7. Identify, test, develop and use HCV animal models, including surrogates,
to evaluate neutralizing antibodies, and as screening systems for new
antiviral agents.
8. Identify and define a receptor / receptor complex for HCV.
Clinical Studies
To address objectives 1-4 effectively and to determine the clinical relevance
of any observations, it is necessary, in parallel, to undertake clinical
studies in well defined cohorts of patients in whom HCV infection, clearance
or persistence, and the progression of liver disease can be meaningfully and
systematically studied, with particular reference to immunological
parameters. Such patient cohorts include, but may not be limited to, those
infected during intravenous drug abuse, minority populations who may be more
susceptible to chronic infection and liver disease, those who show poor
response to interferon therapy, and those co-infected with HIV. Therefore,
applications for studying questions 1-4 in ”Objectives and Scope” must
contain an integrated, scientifically related, clinical project.
Exclusions
This RFA is not intended to support basic molecular studies on the
replication of HCV RNA or HCV protein expression, or their regulation, unless
such studies are demonstrated to relate directly to the purposes of this RFA,
as outlined. Studies involving the use of genomic or proteomic technologies
will only be considered if a credible and logical plan is presented for
analyzing and applying the results to furthering the objectives of this RFA.
In addition, clinical trials for new drugs or vaccine candidates will not be
supported under this RFA. However, research questions that are best addressed
by studying clinical specimens from or in patients in defined populations or
cohorts are especially encouraged.
CRC Research Component: A CRC must consist of two or more related,
multidisciplinary projects utilizing molecular biological and immunological
approaches. These approaches may include experiments using animals such as
mice, macaque monkeys and chimpanzees. Each project must be led by a Project
Leader. These projects may or may not be within the same institution. The
CRC Director must be the Project Leader at the applicant organization, and
will have responsibility for the scientific direction, coordination, and
administrative management of the CRC.
Scientific Core: Scientific core facilities/resources may be proposed if
they will be utilized by at least two of the research projects. Resources
include reagents (e.g., antibodies, peptides, etc.), special technology and
databases. Scientific cores should be well justified and clearly non-
duplicative of other services or facilities available to the CRC
investigators. If appropriate to the particular CRC, repositories for cells,
tissues, reagents, or large data sets may be funded as Core Facilities. In
this case, applications should include methods to obtain, protect and archive
relevant clinical and family history information.
Administrative Core: An Administrative Core is required for the management
of the CRC program. The Administrative Core should include plans for
organization, decision-making, periodic evaluations within the CRC, and data
sharing. An Administrative Core budget should be included to provide for the
required support staff, preparation of manuscripts for publication,
telecommunications, and travel for participation in annual meetings of the
CRCs (see SPECIAL REQUIREMENTS section below for annual meetings).
MECHANISM OF SUPPORT
This RFA will use the NIH multi-project cooperative agreement (U19), an
"assistance" mechanism, rather than an "acquisition" mechanism. The applicant
will be solely responsible for planning, directing, and executing the
proposed project. This RFA is a one-time solicitation. Future unsolicited,
competing-continuation applications based on this project will compete with
all investigator-initiated applications and will be reviewed according to the
customary peer review procedures. The anticipated award date is June 30,
2005. Applications that are not funded in the competition described in this
RFA may be resubmitted as NEW investigator-initiated applications using the
standard receipt dates for NEW applications described in the instructions to
the PHS 398 application.
The NIH U19 is a cooperative agreement award mechanism in which the Principal
Investigator retains the primary responsibility and dominant role for
planning, directing, and executing the proposed project, with NIH staff being
substantially involved as a partner with the Principal Investigator, as
described under the section "Cooperative Agreement Terms and Conditions of
Award”. The total project period for applications submitted in response to
this RFA may not exceed five years.
This RFA uses just-in-time concepts. It also uses the modular budgeting as
well as the non-modular budgeting formats (see
http://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, if
the investigator is submitting an application with direct costs in each year
of $250,000 or less, use the modular budget format. Otherwise follow the
instructions for non-modular budget research grant applications. This program
does not require cost sharing as defined in the current NIH Grants Policy
Statement at
http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm.
Applicants for U19 grants must follow special application guidelines in the
NIAID Brochure entitled INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT
AWARDS; this brochure is available via the WWW at
http://www.niaid.nih.gov/ncn/grants/multibron.htm.
FUNDS AVAILABLE
The participating ICs intend to commit approximately $6,400,000 in FY 2005 to
fund 5 to 7 new and/or competing continuation grants in response to this RFA.
An applicant may request a project period of up to 5 years and a budget for
total costs of up to $1,250,000 per year. Because the nature and scope of the
proposed research will vary from application to application, it is
anticipated that the size and duration of each award will also vary. Although
the financial plans of the ICs provide support for this program, awards
pursuant to this RFA are contingent upon the availability of funds and the
receipt of a sufficient number of meritorious applications. Funding for the
Development Program for Pilot Projects is in addition to the total costs.
Details on the Development Program are provided in the “SPECIAL REQUIREMENTS”
section below.
At this time, the NIAID has not determined whether or how this solicitation
will be continued beyond the present RFA.
ELIGIBLE INSTITUTIONS
The applicant may submit (an) application(s) if the institution has any of
the following characteristics:
o For-profit or non-profit organizations
o Public or private institutions, such as universities, colleges, hospitals,
and laboratories
o Units of State and local governments
o Eligible agencies of the Federal government
o Domestic institutions/organizations
o Foreign institutions are not eligible to apply, but may be part of a
collaborative arrangement.
o Faith-based or community-based organizations
INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS
Any individual with the skills, knowledge, and resources necessary to carry
out the proposed research is invited to work with their institution to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH programs.
SPECIAL REQUIREMENTS
1. Steering Committee
The HC CRC Program Directors and the NIAID Scientific Coordinator will
constitute the Steering Committee for this research program, with
responsibility for reviewing progress and future plans, revising the research
focus if appropriate, and developing collaborative efforts among the
awardees. The Steering Committee and the Project Leaders will meet at least
annually at the NIH in Bethesda, Maryland (or at a site designated by the
NIAID Scientific Coordinator), and will hold quarterly conference calls to
facilitate interaction and collaboration across CRCs. The first such meeting
will be held shortly after award and will be scheduled by the NIAID
Scientific Coordinator. At this meeting, a Steering Committee Chair will be
selected from among the non-Federal members.
Funds for the travel to the annual meetings for the Program Directors,
Project Leaders and other key CRC scientific staff should be included in the
Administrative Core budget.
2. Development Fund (DF) for Pilot Projects
The NIAID has established a CRC DF to respond to unanticipated scientific
needs and opportunities. The goal of the DF is to provide some opportunity
for exploring novel and promising ideas related to the overall objectives of
this RFA – to develop methods or resources to enhance basic and clinical
research, to follow up on new observations and hypotheses, to initiate risky
projects with high potential benefit, or to stimulate collaborative efforts.
Under the DF, an additional $225,000 will be available for Pilot Projects to
a maximum of $75,000 each in direct costs. Each Pilot Project will be funded
for up to 3 years to cover partial salary and research costs. Indirect Costs
will not be allowed for Pilot Projects.
Pilot Projects are not part of the CRC application; therefore, budgets for
Pilot Projects should not be included in the application.
At the initial meeting of the CRC Directors, the Steering Committee will
select one of the CRC Directors to serve as the DF Administrator. The DF
Administrator will appoint a Scientific Review Committee - which includes the
Steering Committee and additional expert(s) from the scientific community as
may be appropriate - to establish criteria for the evaluation of proposed
Pilot Projects, and to solicit, review and select applications for funding.
NIAID approval will be required for the appointment of the Scientific Review
Committee and the final selection of projects for funding. If the quality of
applications received is not deemed to be sufficiently high, NIAID may decide
not to fund any of the projects. Approved projects need not necessarily be
carried out at one of the HC CRCs; however, all Pilot Projects supported must
relate to the specific objectives of this program.
Continued support after the first year will be dependent on review of
satisfactory progress. A separate progress report on each developmental
project must be included in the annual report of the CRC.
3. Clinical Component
In order to undertake basic and clinical approaches in a complementary and
synergistic manner, HC CRCs will need access to well-characterized and
diverse patient samples, as well as clinical experience with populations
representing different disease stages, transmission modes, racial/ethnic
background, co- factors, etc. All applicants are encouraged to include
research utilizing well defined patient cohorts to address clinical questions
and to make correlations with laboratory observations. Applications
addressing one or more of objectives 1-4, as defined under “Objectives and
Scope,” must include a clinical component. For such studies, detailed
proposals, including study objectives, study design, population, clinical
sites, and data analysis plan must be presented in the application.
NIAID encourages: 1) collaborative arrangements with ongoing studies or
clinical care settings capable of providing the crucial patient populations,
specimens and information; and 2) the use of General Clinical Research
Centers (GCRC) facilities supported by the NIH National Center for Research
Resources as a resource for conducting research. If existing studies/cohorts
or GCRC facilities will be used, letters of collaboration or agreement from
the study Principal Investigator or GCRC Program Director respectively must
be included in the application.
4. Sharing of Resources
Restricted availability of unique research resources upon which further
studies are dependent can impede the advancement of research and delivery of
medical care.
NIH policy expects investigators to make unique research resources readily
available for research purposes to qualified individuals within the
scientific community when they have been published [NIH Grants Policy
Statement (http://grants.nih.gov/grants/policy/nihgps/); Principles and
Guidelines for Recipients of NIH Research Grants and Contracts on obtaining
and Disseminating Biomedical Research Resources: Final Notice, December 1999
(http://www.ott.nih.gov/policy/rt_guide_final.html)].
Accordingly, biomaterials and other patentable research resources (e.g.,
genetically encoded reporters, vectors, embryonic cell lines, etc.) produced
in projects funded by this RFA are expected to be made available and
distributed to the broader scientific community.
Intellectual Property Rights
NIH is interested in ensuring that the research resources developed through
this RFA become readily available to the research community. With regard to
patentable research results, such as genetically encoded reporters, cell
lines, and vectors, the NIH expects applicants who respond to this RFA to
develop a plan addressing if, or how, they will exercise their intellectual
property rights while making available to the broader scientific community
research resources produced in projects funded under this RFA. This is
expected to include an elaboration of the applicant’s anticipated plans to
generate, or not generate, patents and/or exclusive or non-exclusive
licensing of biomaterials and other patentable subject matter created in
projects funded under this RFA. This plan should be consistent with the
applicant’s institution’s policies on intellectual property rights.
Applicants are reminded that funding recipients must not enter into any
agreements with third parties that are inconsistent with the terms and
conditions of their NIH award, if awarded, and must revise any agreements
with third parties that are inconsistent with the terms and conditions of an
NIH award to remain in compliance with such NIH award.
The majority of transfers to not-for-profit entities should be implemented
under terms no more restrictive than the Uniform Biological Materials
Transfer Agreement (UBMTA). In particular, recipients are expected to use the
Simple Letter Agreement (SLA) provided at
http://www.ott.nih.gov/policy/rt_guide_final.html, or another document with
no more restrictive terms, to readily transfer unpatented tools developed
with NIH funds to other recipients for use in NIH-funded projects. If the
materials are patented or licensed to an exclusive provider, other
arrangements may be used, but commercialization option rights, royalty reach-
through, or product reach-through rights back to the provider are
inappropriate. Similarly, when for-profit entities are seeking access to NIH-
funded tools for internal use purposes, recipients should ensure that the
tools are transferred with the fewest encumbrances possible. The Simple
Letter Agreement may be expanded for use in transferring tools to for-profit
entities, or simple internal use license agreements with execution or annual
use fees may be appropriate.
Applicants also are reminded that the grantee institution is required to
disclose each subject invention to NIH within two months after the inventor
discloses it in writing to grantee institutional personnel responsible for
patent matters. The awarding institute reserves the right to monitor awardee
activity in this area to ascertain if patents or patent applications on
protocols, cell lines, vectors, or other patentable subject matter are
adversely affecting the goals of this RFA.
As noted earlier, Principles and guidelines for recipients of NIH research
awards on obtaining and disseminating biomedical research resources can be
found at http://www.ott.nih.gov/policy/rt_guide_final.html.
COOPERATIVE AGREEMENT TERMS AND CONDITIONS OF AWARD
The following terms and conditions will be incorporated into the award
statement and provided to the Principal Investigator as well as the
institutional official at the time of award.
These special Terms of Award are in addition to, and not in lieu of,
otherwise applicable OMB administrative guidelines, HHS Grant Administration
Regulations at 45 CFR part 74 and 92, and other HHS, PHS, and NIH Grant
Administration policy statements.
The administrative and funding instrument used for this program is the multi-
project cooperative agreement (U19) an "assistance", rather than an
"acquisition", mechanism, in which substantial NIH scientific and/or
programmatic involvement with the awardee is anticipated during the
performance of the activity. Under the cooperative agreement, the NIH purpose
is to support and/or stimulate the recipient's activity by involvement in and
otherwise working jointly with the award recipient in a partner role, but it
is not to assume direction, prime responsibility, or a dominant role in the
activity. Consistent with this concept, the dominant role and prime
responsibility for the activity resides with the awardees for the project as
a whole, although specific tasks and activities in carrying out the research
will be shared among the awardees and the NIAID Scientific Coordinator.
1. Monitoring Clinical Studies
When clinical studies are a component of the research proposed, NIAID policy
requires that studies be monitored commensurate with the degree of potential
risk to study subjects and the complexity of the study. AN UPDATED NIAID
policy was published in the NIH Guide on July 8, 2002 and is available at:
http://grants.nih.gov/grants/guide/notice-files/NOT-AI-02-032.html. The full
policy, including terms and conditions of award, is available at:
http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf; and the DMID Policies
and Guidance for Data and Safety Monitoring at
http://www.niaid.nih.gov/dmid/clinresearch/. Award of a cooperative agreement
does not constitute approval for initiation of human subjects research. HC
CRC investigators will be required to develop and conduct all studies
involving human subjects using Good Clinical Practice Standards as defined
and published by the International Conference on Harmonization (ICH) and
adopted by the FDA (Federal Register Vol.62 No. 90 (5/9/97) ICH protocol
requirements outlined in part 6 of the ICH Harmonized Tripartite Guideline
for Good Clinical Practice website http://www.ich.org or at
http://www.mch.com/doctors_caregivers/research/Forms/ICH%
20Guidlines%20for%20Research%20Protocols.pdf
2. Awardee Rights and responsibilities
(http://www.fda.gov/oc/gcp/guidance.html).
Prior to study initiation, NIAID staff will review all studies involving
human subjects at two stages. The first stage will be a review of the
research concept and the second review will be during protocol development.
Both stages will be reviewed for scientific content, design, safety,
feasibility, statistical, and regulatory compliance. Use of the NIAID
protocol template, found at the International Clinical Studies Support Center
website (http://icssc.org/rel_links.htm#templates), is encouraged.
Awardees will have primary responsibility for defining the research
objectives, approaches and details of the projects within the guidelines of
the RFA and for performing the scientific activity. Specifically, awardees
have primary responsibility as described below.
It is the primary responsibility of the awardee Program Director to clearly
state the objectives and approaches of the research, to plan and conduct the
research stipulated in the application, and to ensure that the results
obtained are analyzed and published in a timely manner. NIAID may
periodically review and generate internal reports from data and progress
reports developed under this cooperative agreement. The data obtained will,
however, be the property of the awardee.
Awardees will retain custody of and have primary rights to data collected
under this award, subject to Government rights of access consistent with
current U.S. Department of Health and Human Services(DHHS), Public Health
Service(PHS) and National Institutes of health (NIH) Policies.
3. NIAID Staff Responsibilities
NIAID staff assistance will be provided by the Hepatitis Program Officer in
the Enteric and Hepatic Diseases Branch, Division of Microbiology and
Infectious Diseases, who will serve as the NIAID Scientific Coordinator. The
NIAID Scientific Coordinator will have substantial scientific/programmatic
involvement during the conduct of this activity through technical assistance,
advice and coordination above and beyond normal program stewardship for
grants, particularly with regard to the following aspects:
Participation as a member of the HC CRC Steering Committee and attendance at
annual Steering Committee meetings;
Participation as a member of the Scientific Review Committee to evaluate and
select Pilot Projects for funding;
Overall design of studies, especially those undertaken jointly by the HC
CRC’s linkage to special populations;
NIAID staff will also facilitate liaison with existing NIAID contracts and
interaction with other investigators within and outside the HC CRCs for:
vaccine production; data collection and analysis; HCV reagent repository;
resource and reagent sharing; HCV sequence database; and pedigreed specimen
exchange.
The NIAID Scientific Coordinator will serve as a liaison/facilitator between
the awardee, pharmaceutical and biotechnology companies, and other government
agencies (e.g., the U.S. Food and Drug Administration (FDA), the U.S.
Department of Agriculture, the Centers for Disease Control and Prevention)
and will serve as a resource for scientific and policy information related to
the goals of the awardee's research. However, the role of NIAID will be to
facilitate and not to direct the activities. It is anticipated that decisions
in all activities will be reached by consensus and the NIAID staff will be
given the opportunity to offer input into this process. The manner of
reaching this consensus and the final decision-making authority will rest
with the Principal Investigator.
An NIAID Program Official will be assigned to perform normal program
stewardship responsibilities for this award. The Program Official may serve
as the NIAID Scientific Coordinator.
4. Collaborative Responsibilities
The HC CRC Program Directors and the NIAID Scientific Coordinator will
constitute the Steering Committee for this research program and will meet at
least annually to review progress and future plans, revise the focus if
required, and develop collaborative efforts.
The NIAID Scientific Coordinator will work with the HC CRC Program Director
selected to serve as the Development Fund Administrator to appoint a
Scientific Review Committee; both will participate in the review and
selection of applications for Pilot Projects.
Special Consideration: In the event that research supported by the
Cooperative Agreement results in development of a therapeutic or other
medical intervention, NIAID will retain the option to cross-file or
independently file an application for an investigational clinical trial
(i.e., an Investigational New Drug Application [IND]) to the FDA. To
facilitate this, reports of data generated by the HC CRCs or any of its
members, which are required for inclusion in INDs and Clinical Brochures and
for cross-filing purposes, will be submitted by the Program Director to the
NIAID Scientific Coordinator upon request. Such reports will be in final
draft form and include background information, methods, results, and
conclusions. They will be subject to approval and revision by NIAID and may
be augmented with test results from other Government-sponsored projects prior
to submission to the appropriate regulatory agency.
5. Arbitration
Any disagreement that may arise on scientific/programmatic matters (within
the scope of the award) between award recipients and I/C may be brought to
arbitration. An arbitration panel will be composed of three members – one
chosen by the awardee, a second member selected by the IC, and the third
member selected by the two prior selected members. This special arbitration
procedure in no way affects the awardee's right to appeal an adverse action
that is otherwise appealable in accordance with the PHS regulations at 42 CFR
Part 50, Subpart D and HHS regulation at 45 CFR Part 16.
These special Terms of Award are in addition to and not in lieu of otherwise
applicable OMB administrative guidelines, HHS Grant Administration
Regulations at 45 CFR Parts 74 and 92, and other HHS, PHS, and NIH Grant
Administration policy statements.
WHERE TO SEND INQUIRIES
We encourage inquiries concerning this RFA and welcome the opportunity to
answer questions from potential applicants. Inquiries may fall into three
areas: scientific/research, peer review, and financial or grants management
issues.
o Direct questions about scientific/research issues to:
Rajen Koshy, PhD
Enteric and Hepatic Diseases Branch
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases
Room Number 4010, MSC-6603
6610 Rockledge Drive
Bethesda, MD 20892-6603
Telephone: 301 402 8550
FAX: 301 402 1456
Email: rk133f@nih.gov
o Direct questions about peer review issues to:
Gerald McLaughlin
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3119, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
Telephone: (301) 435-2766
FAX: (301) 402-2638
Email: gm145a@nih.gov
o Direct questions about financial or grants management matters to:
Celeste Kerner
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2253, MSC-7614
6700-B Rockledge Drive
Bethesda, MD 20892-7614
Telephone: (301) 402-6213
FAX: (301) 480-3780
Email: ck103k@nih.gov
LETTER OF INTENT
Prospective applicants are asked to submit a letter of intent that includes
the following information:
o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel
o Participating institutions
o Number and title of this RFA
Although a letter of intent is not required, is not binding, and does not
enter into the review of a subsequent application, the information that it
contains allows IC staff to estimate the potential review workload and plan
the review.
The letter of intent is to be sent by the date listed at the beginning of
this document. The letter of intent should be sent to:
Gerald McLaughlin
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3119, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
Telephone: (301) 435-2766
FAX: (301) 402-2638
Email: gm145a@nih.gov
SUBMITTING AN APPLICATION
Applicants for U19 grants must follow special application guidelines in the
NIAID Brochure entitled INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT
AWARDS; this brochure is available via the WWW at
http://www.niaid.nih.gov/ncn/grants/multibron.htm.
Applications must be prepared using the PHS 398 research grant application
instructions and forms (rev. 5/2001). Applications must have a DUN and
Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the
Universal Identifier when applying for Federal grants or cooperative
agreements. The D&B number can be obtained by calling (866) 705-5711 or
through the web site at http://www.dunandbradstreet.com/. The D&B number
should be entered on line 11 of the face page of the PHS 398 form. The PHS
398 document is available at
http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive
format. For further assistance contact GrantsInfo, Telephone (301) 435-0714,
Email: GrantsInfo@nih.gov.
USING THE RFA LABEL: The RFA label, available in the PHS 398 (rev. 5/2001),
application form, must be affixed to the bottom of the face page of the
application. Type the RFA number on the label. Failure to use this label
could result in delayed processing of the application such that it may not
reach the review committee in time for review. In addition, the RFA title and
number must be typed on line 2 of the face page of the application form and
the YES box must be marked. The RFA label is also available at
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of
the application, including the Checklist, and three signed, photocopies, in
one package to:
Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive
Room 1040, MSC 7710
Bethesda, MD 20892-7710
Bethesda, MD 20817 (for express/courier service)
At the time of submission, two additional exact copies of the grant
application and all five sets of any appendix material must be sent to:
Gerald McLaughlin
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3119, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
BETHESDA, MD 20817 (for express mail or courier service)
Applications that are not received as a single package on or before November
22, 2004 or that do not conform to the instructions contained in PHS 398
(rev. 5/01) Application Kit (as modified in, and superseded by, the NIAID
BROCHURE ENTITLED "INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT AWARDS"),
will be judged non-responsive and will be returned to the applicant.
SPECIAL INSTRUCTIONS FOR COMPLETION OF APPLICATIONS IN RESPONSE TO THIS RFA:
Applicants for U19 cooperative agreements must follow special application
guidelines in the NIAID Brochure entitled INSTRUCTIONS FOR APPLICATIONS FOR
MULTI-PROJECT AWARDS; this brochure is available from NIAID listed under
INQUIRIES via the WWW at http://www.niaid.nih.gov/ncn/grants/multibron.htm.
This brochure presents specific instructions for sections of the PHS 398
(rev. 5/01) application form that should be completed differently than usual.
For all other items in the application, follow the usual instructions in the
PHS 398.
APPLICATION PROCESSING: Applications must be received by the application
receipt date listed in the heading of this RFA. If an application is received
after that date, it will be returned to the applicant without review.
The NIH will not accept any application in response to this RFA that is
essentially the same as one currently pending initial review, unless the
applicant withdraws the pending application. However, when a previously
unfunded application, originally submitted as an investigator-initiated
application, is to be submitted in response to an RFA, it is to be prepared
as a NEW application. That is the application for the RFA must not include an
Introduction describing the changes and improvements made, and the text must
not be marked to indicate the changes from the previous unfunded version of
the application. While the investigator may still benefit from the previous
review, the RFA application is not to state explicitly how.
CONCURRENT SUBMISSION OF AN R01 AND A COMPONENT PROJECT OF A MULTI-PROJECT
APPLICATION: Current NIH policy permits a component research project of a
multi-project grant application to be concurrently submitted as a traditional
individual research project (R01) application. If, following review, both the
multi-project application and the R01 application are found to be in the
fundable range, the investigator must relinquish the R01 and will not have
the option to withdraw from the multi-project grant. This is an NIH policy
intended to preserve the scientific integrity of a multi-project grant, which
may be seriously compromised if a strong component project(s) is removed from
the program. Investigators wishing to participate in a multi-project grant
must be aware of this policy before making a commitment to the Principal
Investigator and awarding institution.
Although there is no immediate acknowledgement of the receipt of an
application, applicants are generally notified of the review and funding
assignment within 8 weeks.
PEER REVIEW PROCESS
Upon receipt, applications will be reviewed for completeness by the CSR and
responsiveness by the NIAID.
Incomplete and/or non-responsive applications will be returned to the
applicant without further consideration. Applications that are complete and
responsive to the RFA will be evaluated for scientific and technical merit by
an appropriate peer review group convened by the NIAID in accordance with the
review criteria stated below. As part of the initial merit review, all
applications will:
o Undergo a selection process in which only those applications deemed to have
the highest scientific merit, generally the top half of applications under
review, will be discussed and assigned a priority score
o Receive a written critique
o Receive a second level review by the National Advisory Allergy and
Infectious Diseases Council
REVIEW CRITERIA
The general review criteria for U19 multi-project cooperative agreement
applications are presented in the NIAID brochure entitled "INSTRUCTIONS FOR
APPLICATIONS FOR MULTI-PROJECT AWARDS” at
http://www.niaid.nih.gov/ncn/grants/multibron.htm.
PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of human
subjects and protections from research risk relating to their participation
in the proposed research will be assessed. (See criteria included in the
section on Federal Citations, below)
INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy of
plans to include subjects from both genders, all racial and ethnic groups
(and subgroups), and children as appropriate for the scientific goals of the
research. Plans for the recruitment and retention of subjects will also be
evaluated. (See Inclusion Criteria in the sections on Federal Citations,
below).
CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals are to
be used in the project, the five items described under Section f of the PHS
398 research grant application instructions (rev. 5/2001) will be assessed.
ADDITIONAL REVIEW CONSIDERATIONS
SHARING RESEARCH DATA: Applicants requesting $500,000 or more in direct
costs, in any year of the proposed research, are expected to include a data
sharing plan in their application. The reasonableness of the data sharing
plan or the rationale for not sharing research data will be assessed by the
reviewers. However, reviewers will not factor the proposed data-sharing plan
into the determination of scientific merit or priority score. (See
instructions and URL to policy in the Federal Citations, below.)
BUDGET: The reasonableness of the proposed budget and the requested period of
support in relation to the proposed research.
RECEIPT AND REVIEW SCHEDULE
Letter of Intent Receipt Date: October 22, 2004
Application Receipt Date: November 22, 2004
Peer Review Date: March 15, 2005
Council Review: May 2005
Earliest Anticipated Start Date: June 30, 2005
AWARD CRITERIA
Award criteria that will be used to make award decisions include:
o Scientific merit of the proposed project as determined by peer review
o Availability of funds
o Programmatic priorities.
REQUIRED FEDERAL CITATIONS
ANIMAL WELFARE PROTECTION: Recipients of PHS support for activities
involving live, vertebrate animals must comply with PHS Policy on Humane Care
and Use of Laboratory Animals
(http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf), as
mandated by the Health Research Extension Act of 1985
(http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA
Animal Welfare Regulations
(http://www.nal.usda.gov/awic/legislat/usdaleg1.htm), as applicable.
HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that
applications and proposals involving human subjects must be evaluated with
reference to the risks to the subjects, the adequacy of protection against
these risks, the potential benefits of the research to the subjects and
others, and the importance of the knowledge gained or to be gained.
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm
DATA AND SAFETY MONITORING PLAN: Data and safety monitoring is required for
all types of clinical trials, including physiologic, toxicity, and dose-
finding studies (phase I); efficacy studies (phase II), efficacy,
effectiveness and comparative trials (phase III). The establishment of data
and safety monitoring boards (DSMBs) is required for multi-site clinical
trials involving interventions that entail potential risk to the
participants. (NIH Policy for Data Safety and Monitoring, NIH Guide for
Grants and Contracts, June 12, 1998):
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).
SHARING RESEARCH DATA: Investigators submitting an NIH application seeking
$500,000 or more in direct costs in any single year are expected to include a
plan for data sharing or state why this is not possible
http://grants.nih.gov/grants/policy/data_sharing. Investigators should seek
guidance from their institutions, on issues related to institutional
policies, local IRB rules, as well as local, state and Federal laws and
regulations, including the Privacy Rule. Reviewers will consider the data
sharing plan but will not factor the plan into the determination of the
scientific merit or the priority score.
INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy of
the NIH that women and members of minority groups and their sub-populations
must be included in all NIH-supported clinical research projects unless a
clear and compelling justification is provided indicating that inclusion is
inappropriate with respect to the health of the subjects or the purpose of
the research. This policy results from the NIH Revitalization Act of 1993,
(Section 492B of Public Law 103-43).
All investigators proposing clinical research should read the AMENDMENT "NIH
Guidelines for Inclusion of Women and Minorities as Subjects in Clinical
Research - Amended, October, 2001," published in the NIH Guide for Grants and
Contracts on October 9, 2001
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines are available at
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical
research; updated racial and ethnic categories in compliance with the new OMB
standards; clarification of language governing NIH-defined Phase III clinical
trials consistent with the new PHS Form 398; and updated roles and
responsibilities of NIH staff and the extramural community. The policy
continues to require for all NIH-defined Phase III clinical trials that: a)
all applications or proposals and/or protocols must provide a description of
plans to conduct analyses, as appropriate, to address differences by
sex/gender and/or racial/ethnic groups, including subgroups if applicable;
and b) investigators must report annual accrual and progress in conducting
analyses, as appropriate, by sex/gender and/or racial/ethnic group
differences.
INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS:
The NIH maintains a policy that children (i.e., individuals under the age of
21) must be included in all human subjects research, conducted or supported
by the NIH, unless there are scientific and ethical reasons not to include
them.
All investigators proposing research involving human subjects should read the
"NIH Policy and Guidelines" on the inclusion of children as participants in
research involving human subjects that is available at
http://grants.nih.gov/grants/funding/children/children.htm.
REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH
policy requires education on the protection of human subject participants for
all investigators submitting NIH proposals for research involving human
subjects. This policy announcement is in the NIH Guide for Grants and
Contracts Announcement, dated June 5, 2000, at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.
HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research
on hESCs can be found at http://stemcells.nih.gov/index.asp and at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only
research using hESC lines that are registered in the NIH Human Embryonic Stem
Cell Registry will be eligible for Federal funding (see http://escr.nih.gov).
It is the responsibility of the applicant to provide, in the project
description and elsewhere in the application as appropriate, the official NIH
identifier(s) for the hESC line(s) to be used in the proposed research.
Applications that do not provide this information will be returned without
review.
PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The
Office of Management and Budget (OMB) Circular A-110 has been revised to
provide public access to research data through the Freedom of Information Act
(FOIA) under some circumstances. Data that are (1) first produced in a
project that is supported in whole or in part with Federal funds and (2)
cited publicly and officially by a Federal agency in support of an action
that has the force and effect of law (i.e., a regulation) may be accessed
through FOIA. It is important for applicants to understand the basic scope of
this amendment. NIH has provided guidance at
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.
Applicants may wish to place data collected under this RFA in a public
archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application should
include a description of the archiving plan in the study design and include
information about this in the budget justification section of the
application. In addition, applicants should think about how to structure
informed consent statements and other human subjects procedures given the
potential for wider use of data collected under this award.
STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION: The
Department of Health and Human Services (DHHS) issued final modification to
the “Standards for Privacy of Individually Identifiable Health Information”,
the “Privacy Rule,” on August 14, 2002. The Privacy Rule is a federal
regulation under the Health Insurance Portability and Accountability Act
(HIPAA) of 1996 that governs the protection of individually identifiable
health information, and is administered and enforced by the DHHS Office for
Civil Rights (OCR).
Decisions about applicability and implementation of the Privacy Rule reside
with the researcher and his/her institution. The OCR website
(http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including
a complete Regulation Text and a set of decision tools on “Am I a covered
entity?” Information on the impact of the HIPAA Privacy Rule on NIH processes
involving the review, funding, and progress monitoring of grants, cooperative
agreements, and research contracts can be found at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.
URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals
for NIH funding must be self-contained within specified page limitations.
Unless otherwise specified in an NIH solicitation, Internet addresses (URLs)
should not be used to provide information necessary to the review because
reviewers are under no obligation to view the Internet sites. Furthermore, we
caution reviewers that their anonymity may be compromised when they directly
access an Internet site.
HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to
achieving the health promotion and disease prevention objectives of "Healthy
People 2010," a PHS-led national activity for setting priority areas. This
RFA is related to one or more of the priority areas. Potential applicants may
obtain a copy of "Healthy People 2010" at
http://www.health.gov/healthypeople.
AUTHORITY AND REGULATIONS
This program is described in the Catalogue of Federal Domestic Assistance at
http://www.cfda.gov/ in the following citations: No. 93.855, Immunology,
Allergy, Transplantation Research; No. 93.856, Microbiology and Infectious
Diseases Research; and No. 93.848, Digestive Diseases and Nutrition Research.
Awards are made under authorization of Sections 301 and 405 of the Public
Health Service Act as amended (42 USC 241 and 284) and administered under NIH
grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92.
This program is not subject to the intergovernmental review requirements of
Executive Order 12372 or Health Systems Agency review.
The NIH Grants Policy Statement is available at
http://grants.nih.gov/grants/policy/policy.htm. This document includes
general information about the grant application and review process;
information on the terms and conditions that apply to NIH Grants and
cooperative agreements; and a listing of pertinent offices and officials at
the NIH. All awards are subject to the terms and conditions, cost principles,
and other considerations described in the NIH Grants Policy Statement.
The PHS strongly encourages all grant recipients to provide a smoke-free
workplace and discourage the use of all tobacco products. In addition, Public
Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain
facilities (or in some cases, any portion of a facility) in which regular or
routine education, library, day care, health care, or early childhood
development services are provided to children. This is consistent with the
PHS mission to protect and advance the physical and mental health of the
American people.